Update: The following update relating to this announcement has been issued:

August 16, 2010 - IMPORTANT NOTE! NIH has eliminated the error correction window for due dates of January 25, 2011 and beyond. As of January 25, all corrections
must be complete by the due date for an application to be considered on-time. See NOT-OD-10-123.

January 12, 2010 - See Notice NOT-CA-10-014 This Notice is to inform applicants that the National Cancer Institute announces its participation, effective immediately.

Request for
Applications (RFA) Number: RFA-OD-10-008

NOTICE: Applications submitted in response to this
Funding Opportunity Announcement (FOA) for Federal assistance must be submitted
electronically through Grants.gov (http://www.grants.gov) using the SF424
Research and Related (R&R) forms and the SF424 (R&R) Application Guide.

APPLICATIONS MAY NOT
BE SUBMITTED IN PAPER FORMAT.

This FOA must be read in
conjunction with the application guidelines included with this announcement in Grants.gov/Apply
for Grants (hereafter called Grants.gov/Apply).

A registration process
is necessary before submission and applicants are highly encouraged to start
the process at least four (4) weeks prior to the grant submission date. See Section IV.

Purpose. This
NIH Funding
Opportunity Announcement (FOA), supported by funds provided to the NIH under the American Recovery & Reinvestment
Act of 2009 (“Recovery Act” or “ARRA”), Public
Law 111-5, invites applications to conduct preliminary comparative effectiveness
research (CER) projects in targeted, high-priority areas in which such efforts
have been lacking. (For this FOA, applications should be thought of as large
pilot or preliminary studies rather than definitive trials.) For the purposes
of this FOA, the definition of comparative effectiveness research will adhere
to that adopted by the Federal Coordinating Council given at
http://www.hhs.gov/recovery/programs/cer/execsummary.html.

Mechanism of Support. This FOA will use the ARRA-specific NIH mechanism RC4.

Funds Available and Anticipated Number of
Awards. The NIH intends to commit $15,000,000 for use under this FOA, $5,000,000 in each of the 3 targeted areas. We
anticipate that 4-6 awards
will be made in each area for fiscal year 2010, pending
the number and quality of applications and availability of funds.

Budget and Project Period. Total
costs are limited to a cumulative total of $1,250,000 throughout the grant
period. The total project period for an application submitted in response to
this funding opportunity may not exceed three years.

Research Strategy
Component Length: The RC4
application Research Strategy component of the PHS398 (Items 3-5) may not
exceed 12 pages, including tables, graphs, figures, diagrams, and charts.

Eligible Institutions/Organizations. Institutions/organizations
listed in Section III, 1.A. are eligible to apply. Foreign
institutions/organizations are not eligible to apply.

Eligible Project Directors/Principal Investigators (PDs/PIs). Individuals
with the skills, knowledge, and resources necessary to carry out the proposed
research are invited to work with their institution/ organization to develop an
application for support. Individuals from underrepresented racial and ethnic
groups as well as individuals with disabilities are always encouraged to apply
for NIH support.

Number
of PDs/PIs. More than one PD/PI (i.e., multiple PDs/PIs) may be designated on the
application

Number
of Applications. Applicants may submit more than one application, provided
each application is scientifically distinct.

Resubmissions. Because
this is a one-time-only solicitation, resubmissions are not permitted.

This
FOA invites applications to conduct initial or preliminary comparative
effectiveness research (CER) projects in targeted, high-priority areas in which
such efforts have been lacking. CER encompasses a wide array of methodologies,
including technology assessment, meta-analysis, systematic reviews,
observational studies, and experimental trials. For the purposes of this FOA,
the definition of comparative effectiveness research will adhere to that
adopted by the Federal Coordinating Council given at http://www.hhs.gov/recovery/programs/cer/execsummary.html: “Comparative
effectiveness research is the conduct and synthesis of research comparing the
benefits and harms of different interventions and strategies to prevent,
diagnose, treat and monitor health conditions in “real world” settings. The
purpose of this research is to improve health outcomes by developing and
disseminating evidence-based information to patients, clinicians, and other
decision-makers, responding to their expressed needs, about which interventions
are most effective for which patients under specific circumstances.

To provide this information, comparative effectiveness
research must assess a comprehensive array of health-related outcomes for
diverse patient populations and subgroups.

This research necessitates the development, expansion, and
use of a variety of data sources and methods to assess comparative
effectiveness and actively disseminate the results.”

Priority-Setting Process and Inputs for Use of ARRA OS Funds

There
were four main inputs for priorities for ARRA OS comparative effectiveness
research funds: public input, an internal Departmental workgroup, the FCC
report, and the Institute of Medicine (IOM) report. The FCC identified
the following as minimum threshold criteria which must be met to be considered
for funding:

1)
Included within statutory limits of ARRA and the Council’s definition of
comparative effectiveness research;

2)
Potential to inform decision-making by patients, clinicians or other
stakeholders;

3)
Responsiveness to expressed needs of patients, clinicians or other
stakeholders;

4)
Feasibility of research topic (including time necessary for research).

The
Comparative Effectiveness Research-Coordination and Implementation Team
(CER-CIT) will require the use of the FCC’s prioritization criteria for
scientifically meritorious research and investments for all projects funded
with OS ARRA funds. These criteria are:

3) Addresses
existing uncertainty within the clinical and public health communities
regarding management decisions and variability in practice,

4) Addresses
a need or is unlikely to be addressed through other organizations,
5) Potential for multiplicative effect.

Finally,
investments funded from this appropriation must address at least one of the
following topic areas:

1)
One of the 100 IOM recommendations;

2)
An issue within one the MMA 14 Priority Conditions identified by AHRQ (pursuant
to Section 1013 of the Medicare Prescription Drug Improvement and Modernization
Act of 2003) which are not currently addressed; and/or

Both clinicians and patients are faced with increasingly complex
information about the effects, risks and costs of various health care options.
To assist them with this challenge, comparative effectiveness research (CER)
attempts to provide systematic, well-founded information that will enable them
to engage in informed clinical decision-making. CER holds significant promise
to improve health care quality and potentially lower costs.

For the purposes of this FOA, the definition of comparative
effectiveness research will adhere to that adopted by the Federal Coordinating
Council given at http://www.hhs.gov/recovery/programs/cer/execsummary.html.). The term “comparative” refers to comparisons of interventions
and strategies to prevent, diagnose, treat, and monitor health
conditions. The term “effectiveness” refers to applicability “to
real-world needs and decisions faced by patients, clinicians, and other
decision makers” within “real-world settings,” i.e. not the ideal settings
created in efficacy investigations. CER investigations compare two or
more interventions and strategies that are currently available to practicing
clinicians (i.e., not innovative or experimental drugs, devices, or approaches
that might more typically be part of an FDA-regulated efficacy study).
These interventions and strategies can include “medications, procedures,
medical and assistive devices and technologies, diagnostic testing, behavioral
change, and delivery system strategies.” As examples, CER investigations
could:

Compare two or
more different existing, available drugs for prevention of major morbidity or
mortality in a given medical condition

Compare for a
given medical condition the clinical outcomes of medical and surgical
strategies, where all medications or surgical techniques are already available
in practice

Compare for a
given medical condition the clinical outcomes of existing medical and lifestyle
strategies within the framework of different health care delivery approaches

This
FOA solicits applications on three topics identified in the recent Institute of
Medicine (IOM) report on Initial National Priorities for Comparative
Effectiveness Research (http://www.iom.edu/CMS/3809/63608/71025.aspx) as being in the top quartile of national priorities for CER,
but regarding which there is a paucity of NIH supported CER: upper endoscopy
in Gastroesophageal Reflux Disease (GERD), eradication methods for methicillin
resistant Staphylococcus aureus (MRSA), and strategies for detection and management of
dementia. Applications responsive to this FOA must address the IOM
recommendation pertaining to one of these three areas, but are not limited to
the specific research examples discussed below.

CER
on Upper Endoscopy in Gastroesophageal Reflux Disease (GERD)

Among
digestive diseases, GERD is by far the most common diagnosis at outpatient
visits. Stricture, ulceration, and bleeding are significant non-malignant complications
of GERD. Extraesophageal reflux syndromes of asthma, laryngitis, and cough
commonly co-occur with GERD. The symptoms and diagnosis of GERD are common
among children as well as adults. GERD is strongly associated with Barrett’s
esophagus (intestinal metaplasia in the lower esophagus), but is poor at
predicting who has Barrett’s. As many as half of persons with Barrett’s have
mild or no reflux symptoms and go undiagnosed, and most persons with GERD do
not have Barrett’s. Barrett’s esophagus is the major risk factor found on
endoscopy for adenocarcinoma of the esophagus, although the incidence of cancer
is not high even in the presence of Barrett’s. A finding of dysplasia among
persons with Barrett’s does markedly increase the rate of progression to
cancer. Risk of adenocarcinoma of the esophagus is greatest among middle-age
and older white males. Other factors that define a subset at increased risk
are poorly defined.

Adenocarcinoma
of the esophagus is one of the few malignancies whose incidence is rapidly
increasing. The 5-year survival of patients with esophageal adenocarcinoma is
poor, but it is greatly improved by early endoscopic detection followed by
either resection of the esophagus or endoscopic mucosal ablation. Anti-reflux
therapy with surgery or proton pump inhibitors has not been demonstrated to
reduce the risk of cancer. Some experimental evidence suggests a potential
chemoprotective effect of non-steroidal anti-inflammatory drugs (NSAIDs).

The IOM report has recommended research to “compare the
effectiveness of upper endoscopy utilization and frequency for patients with
gastroesophageal reflux disease on morbidity, quality of life, and diagnosis of
esophageal adenocarcinoma.”

Studies
are needed to address the comparative effectiveness of medications,
anti-reflux surgery, and endoscopic therapies for GERD patients at all
ages. Such research could use existing databases or conduct pilot studies
needed to plan definitive prospective studies.

Minimally
invasive techniques are now available for endoscopic diagnosis and monitoring.
CER pilot and planning studies are needed to determine the relative
effectiveness of trans-nasal and capsule endoscopy in monitoring Barrett’s
esophagus.

CER
studies are needed to determine which uses of diagnostic upper endoscopy and
which patient characteristics among patients with GERD and other indications
for endoscopy are most effective in identifying those with Barrett’s esophagus,
increasing diagnostic yield and reducing the costs of endoscopy. These issues
can be addressed through analyses of existing databases supplemented by limited
additional data collection.

Therapeutic
endoscopic radio-frequency ablation of high-grade dysplasia has been shown to
reduce the incidence of adenocarcinoma of the esophagus. Through existing data
or new pilot data collection, CER studies are needed to compare the outcomes of
ablative therapy with esophageal resection or no therapy for patients with
dysplasia.

Methicillin
resistant Staphylococcus aureus (MRSA) is evolving and emerging both in
the healthcare (hospital and institutions) and in the community setting. The
distinction between strains from these two broadly different compartments is
beginning to blur. Given the public health significance of this species, it is
important to understand the comparative effectiveness of currently available
measures for the prevention and treatment of disease that can result from
encounter with this protean pathogen that also can exist in harmony with the
human host.

The IOM report has recommended research to “compare the
effectiveness of various screening, prophylaxis, and treatment interventions in
eradicating methicillin resistant Staphylococcus aureus (MRSA) in
communities, institutions, and hospitals.”

Particularly
with respect to decolonization of the host, results differ according to
geographical location, location of the patients within the hospital, and
institutional and practice norms. Any assessment of these topics should
carefully consider the relevant variables and represent advance of knowledge
beyond the point of individual primary or comparative (review articles)
literature sources. Applicants are encouraged to review the following links
with information that may be of interest or helpful in preparing applications:

This
solicitation targets proposals that evaluate either pre-existing databases or
the diverse literature to assess any of the following in reducing the incidence
of infection with MRSA in healthcare or community settings:

Studies
submitted in response to this FOA must comprise a rigorous evaluation of the
impact of different options that are available for screening, prophylaxis or
treatment of patients for the purpose of eradication of MRSA for a particular
set of patients. They may compare similar treatments, or may analyze very
different approaches, such as decolonization versus isolation and containment.
Proposed studies should assess the impact on invasive staphylococcal disease,
and address cost effectiveness of the options investigated. For the purposes
of the MRSA eradication priority in this FOA, applications will not be accepted
that involve research which introduces an intervention or that propose new data
collection meeting the NIH definition of a clinical trial: a prospective
biomedical or behavioral research study of human subjects designed to answer
specific questions about biomedical or behavioral interventions (drugs,
treatments, devices, or new ways of using known drugs, treatments, or devices).

CER on Detection and Management Strategies for Dementia
Patients in the Community and Their Caregivers

Recognition
and management of the needs of older adults with dementia living in community
settings constitutes a multifaceted set of issues. A growing body of
literature suggests that dementia detection and diagnosis in primary care is
poor for a number of reasons, including insufficient provider time and
expertise, difficulty managing complex needs of both patient and caregiver, and
low reimbursement for dementia related assessments (Boise, et al., 2004;
Hinton, et al., 2007).

Once
dementias are recognized and diagnosed, clinical management is often as much a
matter of caring for various accompanying neuropsychiatric symptoms and
behavioral disturbances (e.g., depression, anxiety, psychosis, agitation,
aggression) as of treating the individual’s cognitive impairment. However,
recent studies have called into question the effectiveness and safety of the
most typical practice for managing such neuropsychiatric symptoms and
behavioral problems in older adults with dementia – the use of antipsychotic
medications. The effectiveness of these agents appears to be uncertain or
modest at best, and is often offset by intolerable adverse side effects (e.g.,
Jeste, et al., 2008; Salzman, et al., 2008; Schneider, et al, 2006; Sultzer,
et al., 2008). The FDA has issued “black box” warnings that such medications
entail risks for increased mortality in older adults with dementia. Faced with
these uncertainties about prevailing practices, both providers and family
members are eager for better information on the comparative risks and
effectiveness of alternative strategies for caring for older adults with
dementia.

In addition, caregivers are faced with a constantly changing
set of challenges including: understanding the needs and behaviors of the
person with dementia; increasing levels of burden and stress; and lack of time
and/or of awareness of the need to care for themselves. Both behavioral
disturbances and caregiver stress are known to be critical factors influencing
decisions as to whether older adults with dementia can be maintained in the
community or must be placed under institutional care.

The IOM report has recommended research to “compare the
effectiveness and costs of alternative detection and management strategies
(e.g., pharmacologic treatment, social/family support, combined pharmacologic
and social/family support) for dementia in community-dwelling individuals and
their caregivers.”

Various
protocols (including computerized screening measures) that have been developed
for detection and differential diagnosis of dementia in the primary care office
have not been compared for their relative effectiveness or ease of use (e.g.,
Doody, et al., 2001; Knopman, et al., 2001; Petersen, et al., 2001; Waldemar,
2007). Attention should be paid to the validity and reliability of these
protocols, the feasibility of their method of administration, and recommended
treatment steps.

With
respect to managing the care of neuropsychiatric symptoms and behavioral
problems in dementia patients, information is needed on the comparative
effectiveness of various commonly used pharmacological approaches (e.g.,
antipsychotics, antidepressants, benzodiazepines), nonpharmacological
alternatives (e.g., staff and/or family training in behavioral
modification techniques, environmental structuring, somatic and sensorimotor
interventions), and their combinations. Attention should be given
particularly to clarifying the comparative risk-benefit ratios of various interventions
and to their effects on caregivers as well as on the older individuals with
dementia. For purposes of this FOA, NIMH interests are specific to research
addressing these aspects of the topic area.

Several
strategies for reducing informal or family caregiver burden and stress have
been developed, tested, and shown to be effective (e.g., Bell, et al., 2006;
Mittelman, et al.,2006). It is now necessary to test the comparative
effectiveness and cost-effectiveness of these strategies for stress/burden reduction,
as well as their ease of implementation in various settings, including large
scale systems, and ability to postpone institutionalization of the care
recipient.

Studies
are particularly needed that address these issues in racial and ethnic minority
populations and communities. Studies are also need to understand which groups
of patients that are identifiable by a specific cause of dementia or other
shared clinical features will benefit from specific treatment/management
strategies and which do not.

As
many of these issues may ultimately require studies involving multiple research
sites, support under this FOA may be requested for planning appropriate
research protocols and/or building infrastructure elements, such as registries
of dementia patient-caregiver dyads or research networks, needed to conduct
larger, longitudinal CER studies on dementia detection and management
strategies. Support may also be requested for CER studies using archived data
or large administrative data sets in which various outcomes can be compared for
both dementia caregivers and care recipients who have been subjected to
differing protocols for the detection and/or management of dementia and/or for
burden reduction among dementia caregivers.

3.
Scope and Specific Requirements

This
FOA solicits applications for small, 3-year projects proposing analyses of
archival or administrative datasets, pilot clinical trials, observational
studies, planning of future definitive research protocols, building of research
networks or registries, or demonstration projects from multidisciplinary teams
with relevant expertise to conduct CER studies of upper endoscopy in GERD, MRSA
eradication methods, or dementia detection and management strategies. The
research proposed must address the IOM recommendation for studies in the
selected area.

The scope of possible approaches to the CER problems in these
targeted areas has been left open. There are a wide range of valid sources for
information and prior research findings that can support such CER efforts. The
general guideline is that the results of grants following from this FOA should set the
stage for other, future studies definitively establishing the relative
effectiveness of the interventions compared. But such research may be facilitated
or shown feasible as the result of a small-scale randomized clinical trial
(RCT) or clustered randomized trial (CRT), secondary analysis of provider
performance or claims data, an observational study of health care delivery
programs, or other valid methods. Applicants should be aware of the fact that
any proposed project should be feasible within a three year period and a total
costs budget of $1.25 million.

This initiative is supported
by funds provided to the NIH under the American Recovery &
Reinvestment Act of 2009 (“Recovery Act” or “ARRA”), Public Law 111-5. The NIH has designated a cumulative total of $15,000,000 in FY(s) 2010, 2011, and
2012 to fund 12-18 grants (4-6 in each of
the 3 targeted areas), contingent upon the submission of a sufficient number of
scientifically meritorious applications.

The total project period
for an application submitted in response to this funding opportunity may not
exceed 3 years. Although the size of award may vary with the scope of research
proposed, applications must stay within the budgetary guidelines for this FOA;
total costs are limited to $1,250,000 over an RC4 three-year period, with no
more than $500,000 in total costs allowed in any single year. Grants that are
awarded will have to use a non-modular budget. NIH grants policies as described
in the http://era.nih.gov/ElectronicReceipt/preparing.htm for instructions).

The decision of whether to
apply for a grant with a single PD/PI or multiple PDs/PIs is the responsibility
of the investigators and applicant organizations and should be determined by
the scientific goals of the project. Applications for grants with multiple
PDs/PIs will require additional information, as outlined in the instructions
below. When considering the multiple PD/PI option, please be aware that the
structure and governance of the PD/PI leadership team as well as the knowledge,
skills and experience of the individual PDs/PIs will be factored into the
assessment of the overall scientific merit of the application. Multiple
PDs/PIs on a project share the authority and responsibility for leading and
directing the project, intellectually and logistically. Each PD/PI is
responsible and accountable to the grantee organization, or, as appropriate, to
a collaborating organization, for the proper conduct of the project or program,
including the submission of required reports. For further information on
multiple PDs/PIs, please seehttp://grants.nih.gov/grants/multi_pi.

Number of Applications. Applicants may submit more
than one application, provided each application is scientifically distinct.

Resubmissions. Resubmission
applications are not permitted in response to this FOA.

Renewals.Renewal applications are not
permitted in response to this FOA.

Section IV. Application and Submission Information

To
download a SF424 (R&R) Application Package and SF424 (R&R) Application
Guide for completing the SF424 (R&R) forms for this FOA, use the “Apply for
Grant Electronically” button in this FOA or link to http://www.grants.gov/Apply/ and follow the directions provided on that Web site.

Registration:

Appropriate
registrations with Grants.gov and eRA Commons must be completed on or before the
due date in order to successfully submit an application. Several of the
steps of the registration process could take four weeks or more. Therefore,
applicants should immediately check with their business official to determine
whether their organization/institution is already registered with both Grants.gov and the Commons.
All registrations must be complete by the submission deadline for the
application to be considered “on-time” (see 3.C.1 for more information about
on-time submission).

A one-time registration
is required for institutions/organizations at both:

The individual(s) designated as
PDs/PIs on the application must be registered also in the NIH eRA
Commons. In the case of multiple PDs/PIs, all PDs/PIs must be registered and
be assigned the PI role in the eRA Commons prior to the submission of the
application.

Each
PD/PI must hold a PI account in the Commons. Applicants should not share a
Commons account for both a Signing Official (SO) role and a PI role;
however, if they have both a PI role and an Internet Assisted Review (IAR)
role, both roles should exist under one Commons account.

When multiple PDs/PIs are
proposed, all PDs/PIs at the applicant organization must be affiliated with
that organization. PDs/PIs located at another institution need not be
affiliated with the applicant organization, but must be affiliated with their
own organization to be able to access the Commons.

This registration/affiliation must
be done by the AOR/SO or his/her designee who is already registered in the
Commons.

Both the PDs/PI(s) and
AOR/SO need separate accounts in the NIH eRA Commons since both are authorized
to view the application image.

Note: The registration process is not sequential. Applicants should begin
the registration processes for both Grants.gov and eRA Commons as soon as their
organization has obtained a DUNS number. Only one DUNS number is required and
the same DUNS number must be referenced when completing Grants.gov
registration, eRA Commons registration and the SF424 (R&R) forms.

1.
Request Application Information

Applicants must
download the SF424 (R&R) application forms and the SF424 (R&R)
Application Guide for this FOA through Grants.gov/Apply.

Note:
Only the forms package directly attached to a specific FOA can be used. You
will not be able to use any other SF424 (R&R) forms (e.g., sample forms,
forms from another FOA), although some of the "Attachment" files may
be useable for more than one FOA.

Prepare all
applications using the SF424 (R&R) application forms and in accordance with
the SF424 (R&R) Application Guide for this FOA
through Grants.gov/Apply.

The SF424 (R&R)
Application Guide is critical to submitting a complete and accurate application
to NIH. Some fields within the SF424 (R&R) application components, although
not marked as mandatory, are necessary for processing (e.g., the
“Credential” log-in field of the “Research & Related Senior/Key Person
Profile” component must contain the PD/PI’s assigned eRA Commons User ID).
Agency-specific instructions for such fields are clearly identified in the
Application Guide. For additional information, see “Frequently Asked Questions
– Application Guide, Electronic
Submission of Grant Applications.”

The SF424 (R&R)
application has several components. The forms package associated with this FOA
in Grants.gov/APPLYincludes all applicable components, required and optional. A completed
application in response to this FOA includes the data in the following components:

When
multiple PDs/PIs are proposed, NIH requires one PD/PI to be designated as the
"Contact” PI, who will be responsible for all communication between the
PDs/PIs and the NIH, for assembling the application materials outlined below,
and for coordinating progress reports for the project. The contact PD/PI must
meet all eligibility requirements for PD/PI status in the same way as other PDs/PIs,
but has no other special roles or responsibilities within the project team
beyond those mentioned above.

Information
for the Contact PD/PI should be entered in item 15 of the SF424 (R&R) Cover
component. All other PDs/PIs should be listed in the Research &
Related Senior/Key Person component and assigned the project role of
“PD/PI.” Please remember that all PDs/PIs must be registered in the eRA
Commons prior to application submission. The Commons ID of each
PD/PI must be included in the “Credential” field of the Research & Related
Senior/Key Person component. Failure to include this data field will cause
the application to be rejected.

All projects
proposing Multiple PDs/PIs will be required to include a new section describing
the leadership plan approach for
the proposed project.

Multiple
PD/PI Leadership Plan: For applications designating multiple PDs/PIs, the
Research Plan section and Multiple PD/PI Leadership Plan must be included. A
rationale for choosing a multiple PD/PI approach should be described. The
governance and organizational structure of the leadership team and the research
project should be described, and should include communication plans, process
for making decisions on scientific direction, and procedures for resolving
conflicts. The roles and administrative, technical, and scientific
responsibilities for the project or program should be delineated for the
PDs/PIs and other collaborators.

If
budget allocation is planned, the distribution of resources to specific
components of the project or the individual PDs/PIs should be delineated in the
Leadership Plan. In the event of an award, the requested allocations may be
reflected in a footnote on the Notice of Award (NoA).

Applications Involving a
Single Institution

When all PDs/PIs are
within a single institution, follow the instructions contained in the SF424
(R&R) Application Guide.

Applications Involving
Multiple Institutions

When
multiple institutions are involved, one institution must be designated as the
prime institution and funding for the other institution(s) must be requested
via a subcontract to be administered by the prime institution. When submitting
a detailed budget, the prime institution should submit its budget using the
Research & Related Budget component. All other institutions should
have their individual budgets attached separately to the Research & Related
Subaward Budget Attachment(s) Form. See Section 4.8 of the SF424 (R&R)
Application Guide for further instruction regarding the use of the subaward
budget form.

When
submitting a modular budget, the prime institution completes the PHS398 Modular
Budget component only. Information concerning the consortium/subcontract
budget is provided in the budget justification. Separate budgets for each
consortium/subcontract grantee are not required when using the Modular budget
format. See Section 5.4 of the Application Guide for further instruction
regarding the use of the PHS398 Modular Budget component.

To submit an application in response to
this FOA, applicants should access this FOA via http://www.grants.gov/applicants/apply_for_grants.jsp
and follow Steps 1-4. Note: Applications must only be submitted
electronically. PAPER APPLICATIONS WILL NOT BE ACCEPTED. All
attachments must be provided to NIH in PDF format, filenames must be included
with no spaces or special characters, and a .pdf extension must be used.

3.C.
Application Processing

3.C.1 Submitting
On-Time

Applications may be submitted on or after the opening date and must be
successfully received by Grants.gov no later than 5:00 p.m. local
time (of the applicant
institution/organization) on the application due date(s). (See Section
IV.3.A. for all dates.) If an application
is not submitted by the due date(s) and time, the application may be delayed in
the review process or not reviewed.

All
applications must meet the following criteria to be considered “on-time”:

All
registrations must be complete prior to the submission deadline

The application
must receive a Grants.gov traking number and timestamp (or eRA help desk ticket
confirming a system issue preventing submission) by 5:00 p.m. local time on the
submission deadline date.

Any system
identified errors/warnings must be corrected and the submission process
completed within the “error correction window.”

Submission to Grants.gov is not the last step – applicants must follow
their application through to the eRA Commons to check for errors and warnings
and view their assembled application!

3.C.2 Two Day
Window to Correct eRA Identified Errors/Warnings

IMPORTANT NOTE! NIH has eliminated the error correction window for due dates of January 25, 2011 and beyond.
As of January 25, all corrections must be complete by the due date for an application to be considered on-time. See
NOT-OD-10-123.

Once an application package has been
successfully submitted through Grants.gov, NIH provides applicants a two day error
correction window to correct any eRA identified errors or warnings before a
final assembled application is created in the eRA Commons. The standard error
correction window is two (2) business days, beginning the day after the
submission deadline and excluding weekends and standard federal holidays. All
errors must be corrected to successfully complete the submission process.
Warnings will not prevent the application from completing the submission
process.

Please note that the following
caveats apply:

Initial application submission must be “on-time.”

The AOR/institutions is expected to enforce that application
changes made within the error correction window are restricted to those
necessary to address system-identified errors/warnings. NIH may reject any
application that includes additional changes.

Proof of “on-time” submission (e.g., Grants.gov timestamp and
tracking number) and description of all changes made within the window must be
documented in the PHS 398 Cover Letter component of the application.

3.C.3 Viewing
an Application in the eRA Commons

Once any eRA identified errors have been addressed and
the assembled application has been created in the eRA Commons, the PD/PI and the Authorized
Organization Representative/Signing Official (AOR/SO) have two weekdays (Monday
– Friday, excluding Federal holidays) to view the assembled application before it automatically moves forward to NIH for further
processing.

If everything is acceptable, no
further action is necessary. The application will automatically
move forward to the Division of Receipt and Referral in the Center for
Scientific Review for processing after two weekdays, excluding Federal holidays.

Prior to the submission deadline, the
AOR/SO can “Reject” the assembled application and submit a
changed/corrected application within the two-day viewing window. This
option should be used if it is determined that some part of the
application was lost or did not transfer correctly during the submission
process, the AOR/SO will have the option to “Reject” the application and
submit a Changed/Corrected application. In
these cases, please contact the eRA Help Desk to ensure that the issues
are addressed and corrected. Once rejected, applicants should follow the
instructions for correcting errors in Section 2.12 of the SF 424 (R&R)
application guide, including the requirement for cover letters on late
applications. The “Reject” feature should also be used if
you determine that warnings are applicable to your application and need to
be addressed now. Remember, warnings do not stop further application
processing. If an application submission results in warnings (but no
errors), it will automatically move forward after two weekdays if no
action is taken. Some warnings may need to be addressed later in the
process.

If
the two-day window falls after the submission deadline, the AOR/SO will have
the option to “Reject” the application if, due to an eRA Commons or
Grants.gov system issue, the application does not correctly reflect the
submitted application package (e.g., some part of the application was lost or
didn’t transfer correctly during the submission process). The AOR/SO should
first contact the eRA Commons Helpdesk to confirm the system error, document the issue, and
determine the best course of action. NIH will not penalize the applicant for an
eRA Commons or Grants.gov system issue.

If
the AOR/SO chooses to “Reject” the image after the submission deadline for a
reason other than an eRA Commons or Grants.gov system failure, a
changed/corrected application still can be submitted, but it will be subject to
the NIH
late policy guidelines and may not be accepted.
The reason for this delay should be explained in the cover letter attachment.

Both
the AOR/SO and PD/PI will receive e-mail notifications when the application is
rejected or the application automatically moves forward in the process after
two weekdays.

Upon receipt, applications will be evaluated for
completeness by the CSR and responsiveness by the IC. Incomplete and
non-responsive applications will not be reviewed.

There
will be an acknowledgement of receipt of applications from Grants.gov and the Commonshttps://commons.era.nih.gov/commons/. The submitting AOR/SO receives the Grants.gov
acknowledgments. The AOR/SO and the PI receive Commons acknowledgments.
Information related to the assignment of an application to a Scientific Review
Group is also in the Commons.

Note: Since email can be
unreliable, it is the responsibility of the applicant to check periodically on
the application status in the Commons.

The
NIH will not accept any application in response to this funding opportunity
that is essentially the same as one currently pending initial review, unless
the applicant withdraws the pending application. However, when a previously
unfunded application, originally submitted as an investigator-initiated
application, is to be submitted in response to a funding opportunity, it is to
be prepared as a NEW application. That is, the application for the funding
opportunity must not include an “Introduction” describing the changes and
improvements made, and the text must not be marked to indicate the changes from
the previous unfunded version of the application.

4.
Intergovernmental Review

This initiative
is not subject to E.O. 12372 (intergovernmental
review), as indicated
in the NIH Grants Policy Statement.

5. Funding Restrictions

All NIH awards
are subject to the terms and conditions, cost principles, and other
considerations described in the NIH Grants Policy Statement.

Pre-award
costs are allowable. A grantee may, at its own risk and without NIH prior
approval, incur obligations and expenditures to cover costs up to 90 days
before the beginning date of the initial budget period of a new or renewal
award if such costs: 1) are necessary to conduct the project, and 2) would be
allowable under the grant, if awarded, without NIH prior approval. If specific
expenditures would otherwise require prior approval, the grantee must obtain
NIH approval before incurring the cost. NIH prior approval is required for any
costs to be incurred more than 90 days before the beginning date of the initial
budget period of a new or renewal award.

The incurrence of pre-award costs in anticipation of a
competing or non-competing award imposes no obligation on NIH either to make
the award or to increase the amount of the approved budget if an award is made
for less than the amount anticipated and is inadequate to cover the pre-award
costs incurred. NIH expects the grantee to be fully aware that pre-award costs
result in borrowing against future support and that such borrowing must not
impair the grantee's ability to accomplish the project objectives in the
approved time frame or in any way adversely affect the conduct of the project
(see theNIH
Grants Policy Statement).

None of the funds appropriated or otherwise made available
in ARRA may be used by any state or local government, or any private entity,
for any casino or other gambling establishment, aquarium, zoo, golf course, or
swimming pool. (ARRA Sec. 1607)

The applicant organization must include its DUNS number in
its Organization Profile in the eRA Commons. This DUNS number must match the
DUNS number provided at CCR registration with Grants.gov. For additional information, see
“Frequently Asked Questions – Application Guide, Electronic Submission of Grant Applications.”

Special
Instructions for PHS398 Research Strategy Component (Section 5.5 of SF424
(R&R) Application)

Research
Strategy:The Research Strategy is
limited to a total of 12 pages.

PHS398
Research Strategy Component Sections

Item Number
and Title

Instructions

1. Introduction to Application

Omit (N/A: Resubmissions and
Revisions not allowable)

2.
Specific Aims

One
page maximum. Separate PDF attachment

3. Research Strategy

Limited to 12 pages. Attach the 12- page Research Strategy
as a single PDF document. Figures and illustrations may be included but must
fit within the 12-page limit. Do not include links to Web sites for further
information. Do not include animations.

Excluded from the 12-page
Research Strategy limitation are the following items:

Do
not use the Appendix to circumvent the page limitations. An application that
does not comply with the required page limitations may be delayed in the review
process.

No
supplemental/update information will be accepted.

Resource Sharing Plan(s)

NIH
considers the sharing of unique research resources developed through
NIH-sponsored research an important means to enhance the value and further the
advancement of the research. When resources have been developed with NIH funds
and the associated research findings published or provided to NIH, it is
important that they be made readily available for research purposes to
qualified individuals within the scientific community. If the final data/resources are not amenable to sharing,
this must be explained in the Resource Sharing section of the application (see http://grants.nih.gov/grants/policy/data_sharing/data_sharing_faqs.htm).

(b) Sharing Model Organisms: Regardless of
the amount requested, all applications where the development of model organisms
is anticipated are expectedto include a description of a
specific plan for sharing and distributing unique model organisms and related
resources, or state appropriate reasons why such sharing is restricted or not
possible. See Sharing
Model Organisms Policy, and NIH
Guide NOT-OD-04-042.

(c) Genome-Wide Association Studies (GWAS): Regardless of the amount
requested, applicants seeking funding for a genome-wide association
study are expected to provide a plan for submission of GWAS data to the
NIH-designatedGWAS data repository, or provide an appropriate
explanation why submission to the repository is not possible. A
genome-wide association study is defined as any study of genetic variation
across the entire genome that is designed to identify genetic associations with
observable traits (e.g., blood pressure or weight) or the presence or absence
of a disease or condition. For further information see Policy for Sharing
of Data Obtained in NIH Supported or Conducted Genome-Wide Association Studies
(go to NOT-OD-07-088, and http://grants.nih.gov/grants/gwas/.)

Section V. Application Review Information

1.
Criteria

Only
the review criteria described below will be considered in the review process.

2.
Review and Selection Process

Review Process

The mission of the NIH is to support science in pursuit of
knowledge about the biology and behavior of living systems and to apply that
knowledge to extend healthy life and reduce the burdens of illness and
disability. As part of this mission, applications submitted to the NIH
for grants or cooperative agreements to support biomedical and behavioral
research are evaluated for scientific and technical merit through the NIH peer
review system.

Applications that are
complete and
responsive to this FOA will be evaluated for scientific and
technical merit by an appropriate peer review groups convened by the NIH Center for Scientific Review and in accordance with NIH
peer review procedures (http://grants1.nih.gov/grants/peer/), using the review criteria stated below.

As
part of the scientific peer review, all applications will:

Undergo a
selection process in which only those applications deemed to have the
highest scientific and technical merit will be discussed and assigned an
overall impact/priority score;

Receive a
written critique; and

Receive a
second level of review by the National Advisory
Councils of relevant Institutes.

The NIH RC4 grant is a mechanism for supporting research under ARRA.

Overall Impact. Reviewers
will provide an overall impact/priority score to reflect their assessment of
the likelihood for the project to exert a sustained, powerful influence on the
research field(s) involved, in consideration of the following five core review
criteria, and additional review criteria (as applicable for the project
proposed).

Scored Review Criteria. Reviewers
will consider each of the five review criteria below in the determination of
scientific and technical merit, and give a separate score for each. An
application does not need to be strong in all categories to be judged likely to
have major scientific impact. For example, a project that by its nature
is not innovative may be essential to advance a field.

Significance.
Does the project address an important problem or a critical barrier to progress
in the field? If the aims of the project are achieved, how will
scientific knowledge, technological advances, technical capability, clinical
practice, and/or health be improved? How will successful completion of
the aims change the concepts, methods, technologies, treatments, services, or
preventative interventions that drive this field? Would this project help establish
the likelihood that more definitive CER can subsequently be completed in the
research area addressed?

Investigator(s).
Are the PD/PIs, collaborators, and other researchers well suited to the
project? If Early Stage Investigators or New Investigators, do they have
appropriate experience and training? If established, have they
demonstrated an ongoing record of accomplishments that have advanced their
field(s)? If the project is collaborative or multi-PD/PI, do the
investigators have complementary and integrated expertise; are their leadership
approach, governance and organizational structure appropriate for the project? Does the
research team include sufficient expertise in the clinical area addressed and
in CER to allow adequate progress in the accelerated time line required by this
FOA?

Innovation. Does
the application challenge and seek to shift current research or clinical
practice paradigms by utilizing novel theoretical concepts, approaches or
methodologies, instrumentation, or interventions? Are the concepts, approaches
or methodologies, instrumentation, technological developments, or interventions
novel to one field of research or novel in a broad sense? Is a
refinement, improvement, or new application of theoretical concepts, approaches
or methodologies, instrumentation, or interventions proposed?

Approach.
Are the overall strategy, methodology, and analyses well-reasoned and
appropriate to accomplish the specific aims of the project? Are potential
problems, alternative strategies, and benchmarks for success
presented? If the project is in the early stages of development,
will the strategy establish feasibility and will particularly risky aspects be
managed?

If the project involves clinical research, are the plans
for 1) protection of human subjects from research risks, and 2) inclusion of
minorities and members of both sexes/genders, as well as the inclusion of
children, justified in terms of the scientific goals and research strategy
proposed?

Environment. Will the scientific
environment in which the work will be done contribute to the probability of
success? Are the institutional support, equipment and other physical
resources available to the investigators adequate for the project
proposed? Will the project benefit from unique features of the scientific
environment, subject populations, or collaborative arrangements? Will the
applicants be able to obtain access to either patient and/or provider
populations or to the appropriate data sources to complete the proposed work in
the time allowed for by this FOA?

As applicable for the project
proposed, reviewers will consider the following additional items in the
determination of scientific and technical merit, but will not give separate
scores for these items.

Protections for Human Subjects. For
research that involves human subjects but does not involve one of the six
categories of research that are exempt under 45 CFR Part 46, the committee will
evaluate the justification for involvement of human subjects and the proposed
protections from research risk relating to their participation according to the
following five review criteria: 1) risk to subjects, 2) adequacy of protection
against risks, 3) potential benefits to the subjects and others, 4) importance
of the knowledge to be gained, and 5) data and safety monitoring for clinical
trials.

For research that involves human subjects and meets the
criteria for one or more of the six categories of research that are exempt
under 45 CFR Part 46, the committee will evaluate: 1) the justification for the
exemption, 2) human subjects involvement and characteristics, and 3) sources of
materials.

Inclusion of Women, Minorities, and Children.
When the proposed project involves clinical research, the committee will
evaluate the proposed plans for inclusion of minorities and members of both
genders, as well as the inclusion of children.

Vertebrate Animals.
The committee will evaluate the involvement of live vertebrate animals as part
of the scientific assessment according to the following five points: 1)
proposed use of the animals, and species, strains, ages, sex, and numbers to be
used; 2) justifications for the use of animals and for the appropriateness of
the species and numbers proposed; 3) adequacy of veterinary care; 4) procedures
for limiting discomfort, distress, pain and injury to that which is unavoidable
in the conduct of scientifically sound research including the use of analgesic,
anesthetic, and tranquilizing drugs and/or comfortable restraining devices; and
5) methods of euthanasia and reason for selection if not consistent with the
AVMA Guidelines on Euthanasia. For additional information,
see http://grants.nih.gov/grants/olaw/VASchecklist.pdf.

Biohazards.
Reviewers will assess whether materials or procedures proposed are potentially
hazardous to research personnel and/or the environment, and if needed,
determine whether adequate protection is proposed.

2.B. Additional Review Considerations

As applicable for the project proposed, reviewers will
address each of the following items, but will not give scores for these items
and should not consider them in providing an overall impact/priority score.

Select Agents Research. Reviewers will assess the information provided in this section of the
application, including 1) the Select Agent(s) to be used in the proposed
research, 2) the registration status of all entities where Select Agent(s) will
be used, 3) the procedures that will be used to monitor possession, use and
transfer of Select Agent(s), and 4) plans for appropriate biosafety,
biocontainment, and security of the Select Agent(s).

Resource Sharing Plans. Reviewers will
comment on whether the following Resource Sharing Plans, or the rationale for
not sharing the following types of resources, are reasonable:

Budget and Period Support.
Reviewers will consider whether the budget and the requested period of support
are fully justified and reasonable in relation to the proposed research.

Selection Process

Applications
submitted in response to this FOA will compete for available funds with all
other recommended applications submitted in response to this FOA. The following
will be considered in making funding decisions:

Scientific
and technical merit of the proposed project as determined by peer review.

Availability
of funds.

Relevance
of the proposed project to program priorities.

Appeals will not be
permitted. See NOT-OD-09-054,
Recovery Act of 2009: NIH Review Criteria, Scoring System, and Suspension of
Appeals Process.

3.
Anticipated Announcement and Award Dates
Not Applicable

Section
VI. Award Administration Information

1.
Award Notices

After the peer review of the application
is completed, the PD/PI will be able to access his or her Summary Statement
(written critique) via the NIH eRA Commons.

A formal notification in the form of a Notice of Award
(NoA) will be provided to the applicant organization. The NoA signed by the
grants management officer is the authorizing document. Once all administrative
and programmatic issues have been resolved, the NoA will be generated via email
notification from the awarding component to the grantee business official.

The terms of the NoA
will reference the requirements of the Recovery Act.

In addition to the standard NIH terms of award, all awards
will be subject to the HHS Standard Terms and Conditions for Recovery Act
awards. The full text of these terms approved for
NIH awards can be found in the following document: Standard
Terms and Conditions for AARA Awards.

Selection
of an application for award is not an authorization to begin performance. Any
costs incurred before receipt of the NoA are at the recipient's risk. These
costs may be reimbursed only to the extent considered allowable pre-award
costs. See Section
IV.5., “Funding Restrictions.”

In addition, grantees must comply with the requirements set forth in the
Recovery Act, including, but not limited to, the reporting requirements
described in Section 1512 of the Act, as well as applicable OMB guidance
regarding the use of Recovery Act funds. As noted above, grantees must also
comply with the HHS Standard Terms and Conditions for Recovery Act
awards. The full text of these terms approved for NIH awards can be found
in the following document: Standard
Terms and Conditions for AARA Awards.

Recovery Act-related
reporting requirements will be incorporated as a special term of award.

A final progress report, invention statement, and
Financial Status Report are required when an award is relinquished when a
recipient changes institutions or when an award is terminated. Until such time
as HHS has migrated to the SF 425 FFR, award recipients will utilize the SF 269
FSR.

Section VII. Agency Contacts

This funding
announcement is subject to restrictions on oral conversations during the period
of time commencing with the submission of a formal application[1] by an individual or entity and ending with the award of the competitive funds.
Federal officials may not participate in oral communications initiated by any
person or entity concerning a pending application for a Recovery Act
competitive grant or other competitive form of Federal financial assistance,
whether or not the initiating party is a federally registered lobbyist[1].
This restriction applies unless:

(i) the
communication is purely logistical;

(ii) the
communication is made at a widely attended gathering;

(iii) the
communication is to or from a Federal agency official and another Federal
Government employee;

(iv) the
communication is to or from a Federal agency official and an elected chief
executive of a state, local or tribal government, or to or from a Federal
agency official and the Presiding Officer or Majority Leader in each chamber of
a state legislature; or

We
encourage your inquiries concerning this funding opportunity and welcome the
opportunity to answer questions from potential applicants. Inquiries may fall
into three areas: scientific/research (program), peer review, and financial or
grants management issues:

Human Subjects
Protection:Federal regulations (45 CFR 46) require that
applications and proposals involving human subjects must be evaluated with
reference to the risks to the subjects, the adequacy of protection against
these risks, the potential benefits of the research to the subjects and others,
and the importance of the knowledge gained or to be gained (http://www.hhs.gov/ohrp/humansubjects/guidance/45cfr46.htm).

Data and Safety
Monitoring Plan:Data and safety monitoring is required for all types
of clinical trials, including physiologic toxicity and dose-finding studies
(Phase I); efficacy studies (Phase II); efficacy, effectiveness and comparative
trials (Phase III). Monitoring should be commensurate with risk. The
establishment of data and safety monitoring boards (DSMBs) is required for
multi-site clinical trials involving interventions that entail potential risks
to the participants (“NIH Policy for Data and Safety Monitoring,” NIH Guide for Grants and Contracts, http://grants.nih.gov/grants/guide/notice-files/not98-084.html).

Sharing Research Data:Investigators submitting an NIH application seeking
$500,000 or more in direct costs in any single year are expected to include a
plan for data sharing or state why this is not possible (http://grants.nih.gov/grants/policy/data_sharing).Investigators should seek
guidance from their institutions, on issues related to institutional policies
and local institutional review board (IRB) rules, as well as local, State and
Federal laws and regulations, including the Privacy Rule.

Policy for Genome-Wide
Association Studies (GWAS):NIH is interested in advancing genome-wide association
studies (GWAS) to identify common genetic factors that influence health and
disease through a centralized GWAS data repository. For the purposes of this
policy, a genome-wide association study is defined as any study of genetic
variation across the entire human genome that is designed to identify genetic
associations with observable traits (such as blood pressure or weight), or the
presence or absence of a disease or condition. All applications, regardless of
the amount requested, proposing a genome-wide association study are expected to
provide a plan for submission of GWAS data to the NIH-designated GWAS data
repository, or provide an appropriate explanation why submission to the
repository is not possible. Data repository management (submission and access)
is governed by the Policy for Sharing of Data Obtained in NIH Supported or
Conducted Genome-Wide Association Studies, NIH Guide NOT-OD-07-088. For additional information, see http://grants.nih.gov/grants/gwas/.

Sharing of Model Organisms:NIH is committed to support efforts that encourage sharing
of important research resources including the sharing of model organisms for
biomedical research (see http://grants.nih.gov/grants/policy/model_organism/index.htm). At the same time the NIH recognizes the rights of
grantees and contractors to elect and retain title to subject inventions
developed with Federal funding pursuant to the Bayh-Dole Act (see the NIH
Grants Policy Statement. Beginning October 1,
2004, all investigators submitting an NIH application or contract proposal are
expected to include in the application/proposal a description of a specific
plan for sharing and distributing unique model organism research resources
generated using NIH funding or state why such sharing is restricted or not
possible. This will permit other researchers to benefit from the resources
developed with public funding. The inclusion of a model organism sharing plan
is not subject to a cost threshold in any year and is expected to be included
in all applications where the development of model organisms is anticipated.

Access to Research Data through the Freedom of
Information Act:The Office of Management and Budget (OMB) Circular
A-110 has been revised to provide access to research data through the Freedom
of Information Act (FOIA) under some circumstances. Data that are: (1) first
produced in a project that is supported in whole or in part with Federal funds;
and (2) cited publicly and officially by a Federal agency in support of an
action that has the force and effect of law (i.e., a regulation) may be
accessed through FOIA. It is important for applicants to understand the basic
scope of this amendment. NIH has provided guidance at http://grants.nih.gov/grants/policy/a110/a110_guidance_dec1999.htm. Applicants may wish to place data collected under this
funding opportunity in a public archive, which can provide protections for the
data and manage the distribution for an indefinite period of time. If so, the
application should include a description of the archiving plan in the study
design and include information about this in the budget justification section
of the application. In addition, applicants should think about how to structure
informed consent statements and other human subjects procedures given the
potential for wider use of data collected under this award.

Inclusion of Women And Minorities in Clinical Research:It is the policy of the NIH that women and members of
minority groups and their sub-populations must be included in all NIH-supported
clinical research projects unless a clear and compelling justification is
provided indicating that inclusion is inappropriate with respect to the health
of the subjects or the purpose of the research. This policy results from the
NIH Revitalization Act of 1993 (Section 492B of Public Law 103-43). All
investigators proposing clinical research should read the "NIH Guidelines for Inclusion of Women and Minorities as Subjects in Clinical Research” (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-02-001.html); a complete copy of the updated Guidelines is available at http://grants.nih.gov/grants/funding/women_min/guidelines_amended_10_2001.htm. The amended policy incorporates: the use of an NIH
definition of clinical research; updated racial and ethnic categories in
compliance with the new OMB standards; clarification of language governing
NIH-defined Phase III clinical trials consistent with the SF424 (R&R)
application; and updated roles and responsibilities of NIH staff and the
extramural community. The policy continues to require for all NIH-defined Phase
III clinical trials that: a) all applications or proposals and/or protocols
must provide a description of plans to conduct analyses, as appropriate, to
address differences by sex/gender and/or racial/ethnic groups, including
subgroups if applicable; and b) investigators must report annual accrual and
progress in conducting analyses, as appropriate, by sex/gender and/or
racial/ethnic group differences.

Inclusion of Children as Participants in Clinical Research:The NIH maintains a policy that children (i.e.,
individuals under the age of 21) must be included in all clinical research,
conducted or supported by the NIH, unless there are scientific and ethical
reasons not to include them. All investigators proposing research involving
human subjects should read the "NIH Policy and Guidelines" on the
inclusion of children as participants in research involving human subjects (http://grants.nih.gov/grants/funding/children/children.htm).

Required Education on the Protection of Human Subject Participants:NIH policy requires education on the protection of
human subject participants for all investigators submitting NIH applications
for research involving human subjects and individuals designated as key
personnel. The policy is available at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-00-039.html.

Standards for Privacy of Individually Identifiable Health Information:The Department of Health and Human Services (HHS)
issued final modification to the "Standards for Privacy of Individually
Identifiable Health Information", the "Privacy Rule", on August
14, 2002. The Privacy Rule is a federal regulation under the Health Insurance
Portability and Accountability Act (HIPAA) of 1996 that governs the protection
of individually identifiable health information, and is administered and
enforced by the HHS Office for Civil Rights (OCR).

Decisions about applicability and implementation of
the Privacy Rule reside with the researcher and his/her institution. The OCR
website (http://www.hhs.gov/ocr/) provides information on the Privacy Rule, including a
complete Regulation Text and a set of decision tools on "Am I a covered
entity?" Information on the impact of the HIPAA Privacy Rule on NIH
processes involving the review, funding, and progress monitoring of grants,
cooperative agreements, and research contracts can be found at http://grants.nih.gov/grants/guide/notice-files/NOT-OD-03-025.html.

URLs
in NIH Grant Applications or Appendices:All applications and proposals for NIH funding
must be self-contained within specified page limitations. For publications
listed in the appendix and/or Progress report, Internet addresses (URLs) or
PubMed Central (PMC) submission identification numbers must be used for
publicly accessible on-line journal articles. Publicly accessible on-line
journal articles or PMC articles/manuscripts accepted for publication that are
directly relevant to the project may be included only as URLs or PMC
submission identification numbers accompanying the full reference in either
the Bibliography & References Cited section, the Progress Report
Publication List section, or the Biographical Sketch section of the NIH grant
application. A URL or PMC submission identification number citation may be
repeated in each of these sections as appropriate. There is no limit to the
number of URLs or PMC submission identification numbers that can be cited.

Healthy People 2010:The Public Health Service (PHS) is committed to
achieving the health promotion and disease prevention objectives of
"Healthy People 2010," a PHS-led national activity for setting priority
areas. This FOA is related to one or more of the priority areas. Potential
applicants may obtain a copy of "Healthy People 2010" at http://www.health.gov/healthypeople.

Authority and Regulations:This program is described in the Catalog of Federal Domestic Assistance at http://www.cfda.gov/ and
is not subject to the intergovernmental review requirements of Executive Order
12372. Awards are made under Sections 301 and 405 of the PHS Act, as amended
(42 USC 241 and 284) and are subject to 42 CFR Part 52 and 45 CFR Parts 74 and
92. All awards are subject to the terms and conditions, cost principles, and
other considerations described in the NIH Grants
Policy Statement.

The PHS strongly encourages all grant recipients to
provide a smoke-free workplace and discourage the use of all tobacco products.
In addition, Public Law 103-227, the Pro-Children Act of 1994, prohibits
smoking in certain facilities (or in some cases, any portion of a facility) in
which regular or routine education, library, day care, health care, or early
childhood development services are provided to children. This is consistent with
the PHS mission to protect and advance the physical and mental health of the
American people.

Loan Repayment Programs:NIH encourages applications for educational loan
repayment from qualified health professionals who have made a commitment to
pursue a research career involving clinical, pediatric, contraception,
infertility, and health disparities related areas. The LRP is an important
component of NIH's efforts to recruit and retain the next generation of
researchers by providing the means for developing a research career unfettered
by the burden of student loan debt. Note that an NIH grant is not required for
eligibility and concurrent career award and LRP applications are encouraged.
The periods of career award and LRP award may overlap providing the LRP
recipient with the required commitment of time and effort, as LRP awardees must
commit at least 50% of their time (at least 20 hours per week based on a 40
hour week) for two years to the research. For further information, please see: http://www.lrp.nih.gov/.

[1] Formal application includes the preliminary
application and letter of intent phases of the program.